title: Identification and characterization of Cryptosporidium parvum Clec, a novel C-type lectin domain-containing mucin-like glycoprotein.
abstract: Cryptosporidium species are waterborne apicomplexan parasites that cause diarrheal disease worldwide. Although the mechanisms underlying Cryptosporidium-host cell interactions are not well understood, mucin-like glycoproteins of the parasite are known to mediate attachment and invasion in vitro. We identified C. parvum Clec (CpClec), a novel mucin-like glycoprotein that contains a C-type lectin domain (CTLD) and has orthologs in C. hominis and C. muris. CTLD-containing proteins are ligand-binding proteins that function in adhesion and signaling and are present in a wide range of organisms, from humans to viruses. However, this is the first report of a CTLD-containing protein in protozoa and in Apicomplexa. CpClec is predicted to be a type 1 membrane protein, with a CTLD, an O-glycosylated mucin-like domain, a transmembrane domain, and a cytoplasmic tail containing a YXX sorting motif. The predicted structure of CpClec displays several characteristics of canonical CTLD-containing proteins, including a long loop region hydrophobic core associated with calcium-dependent glycan binding as well as predicted calcium- and glycan-binding sites. CpClec expression during C. parvum infection in vitro is maximal at 48 h postinfection, suggesting that it is developmentally regulated. The 120-kDa mass of native CpClec is greater than predicted, most likely due to O-glycosylation. CpClec is localized to the surface of the apical region and to dense granules of sporozoites and merozoites. Taken together, these findings, along with the known functions of C. parvum mucin-like glycoproteins and of CTLD-containing proteins, strongly implicate a significant role for CpClec in Cryptosporidium-host cell interactions.
authors.affiliation: Division of Geographic Medicine and Infectious Diseases, Tufts Medical Center, Boston, Massachusetts, USA.
authors.forename: Seema
authors.initials: S
authors.lastname: Bhalchandra
authors.forename: Jacob
authors.initials: J
authors.lastname: Ludington
authors.forename: Isabelle
authors.initials: I
authors.lastname: Coppens
authors.forename: Honorine D
authors.initials: HD
authors.lastname: Ward
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites / Q000502:physiology; D018938:Caco-2 Cells; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D003457:Cryptosporidiosis / Q000378:metabolism / Q000469:parasitology; D016785:Cryptosporidium parvum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism*; D006031:Glycosylation; D006790:Host-Parasite Interactions / Q000502:physiology; D006801:Humans; D037181:Lectins, C-Type / Q000378:metabolism*; D008024:Ligands; D008565:Membrane Proteins / Q000378:metabolism; D052940:Merozoites / Q000378:metabolism; D008969:Molecular Sequence Data; D009077:Mucins / Q000378:metabolism*; D010802:Phylogeny; D011134:Polysaccharides / Q000378:metabolism; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins / Q000378:metabolism*; D016415:Sequence Alignment; D034101:Sporozoites / Q000378:metabolism
chemical_list: D006023:Glycoproteins; D037181:Lectins, C-Type; D008024:Ligands; D008565:Membrane Proteins; D009077:Mucins; D011134:Polysaccharides; D015800:Protozoan Proteins; D002118:Calcium